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学科主题: 临床医学
题名:
Effects of statin on circulating microRNAome and predicted function regulatory network in patients with unstable anginad
作者: Li, Jingjin1; Chen, Hong1; Ren, Jingyi1; Song, Junxian1; Zhang, Feng1; Zhang, Jing1; Lee, Chongyou1; Li, Sufang1; Geng, Qiang1; Cao, Chengfu1; Xu, Ning2
关键词: Unstable angina ; Statin ; MicroRNA ; System biology ; Regulatory network
刊名: BMC MEDICAL GENOMICS
发表日期: 2015-03-13
DOI: 10.1186/s12920-015-0082-4
卷: 8
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Genetics & Heredity
研究领域[WOS]: Genetics & Heredity
关键词[WOS]: NITRIC-OXIDE SYNTHASE ; HMG-COA REDUCTASE ; RHO-KINASE ; MYOCARDIAL-INFARCTION ; IN-VITRO ; EXPRESSION ; MICE ; ATHEROSCLEROSIS ; INFLAMMATION ; CHOLESTEROL
英文摘要:

Background: Statin therapy plays a pivotal role in stabilizing the plaque for unstable angina (UA) patients although its mechanism(s) remains largely unexplored. Here we aim to identify microRNAs (miRNAs) mediating the protective effect of statins in UA patients.

Methods: MiRNAs Array was carried out to compare the circulating whole blood miRNA profile of UA patients treated with (n = 10) and without statin (n = 10) and plasma miRNA profile UA patients treated with (n = 5) and without statin (n = 5). 22 whole blood miRNAs and 19 plasma miRNAs were found significantly upregulated in statin group. Targets of these miRNAs were predicted by algoritms: Targetscan, Miranda and Diana microT, then clustered according to functions and cell types by using the Database for Annotation, Visualization and Integrated Discovery (DAVID). To reveal the enriched function pathways in human atherosclerotic plaque, we analyzed microarray data from GEO database, Coronary atherosclerotic plaque (n = 80); macrophages in ruptured plaque (n = 11); carotid atheroma plaque (n = 64); advanced carotid atherosclerotic plaque (n = 29) using Reactome database. Integrated analysis indicated that statin induced miRNAs mainly regulate the signaling pathways of Rho GTPase and hemostasis in human atherosclerotic lesion. In vulnerable plaque, additional immune system signaling was also targeted.

Results: The data showed target genes regulated by these statin induced miRNAs majorly expressed in i) plaque macrophage and platelet, where they were involved in hemostasis process; ii) in monocyte to regulate NGF apoptosis; iii) and in endothelial cell function in Rho GTPase pathway. Integrate analysis indicated that statin induced miRNAs mainly regulate the signaling pathways of Rho GTPase and hemostasis in human atherosclerotic lesion.

Conclusions: Our study suggest that statin induces the expression of multiple miRNAs in the circulation of UA patient, which play important roles by regulating signal pathways critical for the pathogenesis of UA.

语种: 英语
所属项目编号: 2012ZX09303019
项目资助者: National science and technology &prime ; creation of major new drugs&prime
WOS记录号: WOS:000351580700001
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/52203
Appears in Collections:北京大学第二临床医学院_心血管内科_期刊论文

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作者单位: 1.Peking Univ, Peoples Hosp, Dept Cardiol, Beijing 100044, Peoples R China
2.Karolinska Inst, Dept Med, Stockholm, Sweden

Recommended Citation:
Li, Jingjin,Chen, Hong,Ren, Jingyi,et al. Effects of statin on circulating microRNAome and predicted function regulatory network in patients with unstable anginad[J]. BMC MEDICAL GENOMICS,2015,8.
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